POGLUT1 gene

The POGLUT1 gene (POGLUT1 stands for: Protein O-Glucosyltransferase 1) is a protein-coding gene located on chromosome 3q13.33. Alternative splicing leads to several transcript variants. Gene Ontology (GO) annotations for this gene include protein xylosyltransferase activity and glucosyltransferase activity. An important paralog of this gene is POGLUT3.

This gene encodes a protein with O-glucosyltransferase and O-xylosyltransferase activity that is localized in the lumen of the endoplasmic reticulum. This protein has a carboxy-terminal KTEL motif, which presumably functions as a retention signal for the endoplasmic reticulum. The POGLUT1 gene is an essential regulator of Notch signaling and likely plays a role in cell fate decision and tissue formation during development. It may also play a role in the pathogenesis of leukemia. The signaling pathways associated with the encoded protein include pre-NOTCH expression and processing and signal transduction.

Glycosyltransferase with dual specificity that catalyzes the transfer of glucose and xylose from UDP-glucose and UDP-xylose to a serine residue present in the consensus sequence C-X-S-X-P-C. Specifically targets extracellular EGF repeats of proteins such as CRB2, F7, F9 and NOTCH2. Acts as a positive regulator of Notch signaling by mediating the O-glucosylation of Notch, which leads to the regulation of muscle development (Servián-Morilla E et al. 2016). Glucosylation of Notch has no effect on the binding of Notch ligands (Fernandez-Valdivia R et al. 2011). Required during early development to promote gastrulation: acts by mediating the O-glucosylation of CRB2, which is required for the localization of CRB2 to the cell membrane.

Mutations in this gene have been associated with the autosomal dominant genodermatosis Dowling-Degos disease. Other diseases associated with POGLUT1 include muscular dystrophy, limb-girdle muscular dystrophy, autosomal recessive 21.

1. Fernandez-Valdivia R et al. (2011) Regulation of mammalian Notch signaling and embryonic development by the protein O-glucosyltransferase Rumi. Development 138:1925-1934.
2. Servián-Morilla E et al. (2016) A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss. EMBO Mol Med 8:1289-1309.